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Vascular cell adhesion molecule 1 (VCAM-1) and E-selectin (or endothelial-leukocyte adhesion molecule 1) are inducible endothelial cell adhesion molecules that play a role in the recruitment of leukocytes into sites of inflammation. Information about the spatial and temporal pattern of induced expression of these leukocyte adhesion molecules in vivo is limited. This study reports the expression profile of VCAM-1 and E-selectin in various mouse tissues after lipopolysaccharide administration. Using rat complementary DNA probes for VCAM-1 and E-selectin, Northern blot analysis showed a marked increase in transcript levels for both adhesion molecules in lung, heart, and kidney. Maximal transcript levels for both VCAM-1 and E-selectin were observed at 3-6 hours and declined to low, constitutive levels of expression at 48 hours. Consistent with the Northern blot results, immunoperoxidase analysis revealed focal endothelial cell expression of VCAM-1 in control animals. Following lipopolysaccharide administration, VCAM-1 expression increased dramatically in all vascular beds examined, although the response was heterogeneous. Widespread induced expression of VCAM-1 on cells other than vascular endothelium was not seen. Neither basal nor induced expression correlated with leukocyte adhesion. Signals other than the expression of endothelial leukocyte adhesion molecules are required in vivo for leukocyte infiltration in this murine model of systemic endothelial activation.

Vascular cell adhesion molecule 1 (VCAM-1)/inducible cell adhesion molecule 110 is a mononuclear leukocyte-selective adhesion molecule, expressed on vascular endothelium following activation by certain cytokines or endotoxin. This inducible transmembrane protein and member of the immunoglobulin gene superfamily was previously reported to contain six immunoglobulinlike domains. Using the polymerase chain reaction, a VCAM-1 cDNA was obtained from mRNA of interleukin-1 (IL-1)-treated cultured human umbilical vein endothelial cells (HUVEC). The cDNA clone contained an additional 276 base-pair (bp) domain, located between domains 3 and 4. This new domain is most homologous to the existing N-terminal domain (domain 1). The internal 276-bp region is encoded by a single exon of the human VCAM-1 gene, indicating that the two forms of mRNA arise by alternative splicing. Both forms of VCAM-1 mRNA were detected by polymerase chain reaction in IL-1-stimulated HUVEC, although the seven-domain form appeared predominant. On the surface of HUVEC only a 110-kd polypeptide, consistent with the seven-immunoglobulinlike domain form of VCAM-1, was detectable by immunoprecipitation. Alternative splicing of the VCAM-1 gene in cytokine-activated endothelium may generate functionally distinct cell-surface adhesion molecules.

The effects of glomerular size and visceral epithelial cell integrity upon the development of progressive glomerulosclerosis was studied by superimposing renal ablation on adriamycin-induced nephropathy in rats. Adriamycin alone caused focal epithelial cell injury and proteinuria but minimal segmental glomerulosclerosis. In normal rats, renal ablation was accompanied by mild progressive proteinuria and glomerulosclerosis. However, renal ablation in rats with adriamycin nephropathy caused a dramatic increase in proteinuria and a disproportionately high frequency of segmental glomerulosclerosis. Accelerated glomerular injury after renal ablation in adriamycin-treated rats was associated with substantial glomerular hypertrophy with near doubling of the tuft volume. Morphometric and autoradiographic studies showed that compensatory glomerular hypertrophy occurs without a proportional increase in the number of visceral epithelial cells, leading to a substantial reduction in the density of these cells within the capillary tuft. The severity of segmental glomerulosclerosis showed a significant correlation with the glomerular volume and the reciprocal of the visceral epithelial cell density. Ultrastructural observations indicate that epithelial defects with detachment of the cell processes from the underlying basement membrane are almost invariably seen in areas of segmental glomerulosclerosis with hyalinosis. These findings suggest that the process of progressive glomerulosclerosis is, to a great extent, contingent upon the development of epithelial cell defects, that result from direct injury or from a reduction in the cell density after inordinate compensatory glomerular hypertrophy.

Chemical carcinogenesis in mouse skin can be divided into the processes of initiation, promotion, and progression. The free-radical generator benzoyl peroxide is moderately active during the promotion stage. Repetitive treatment of mouse benign skin tumors (papillomas) with benzoyl peroxide (20 mg, twice weekly) increased the number of cumulative carcinomas per group by 325% and the number of keratoacanthomas by 44% compared to tumor-bearing Sencar mice treated with the promoter 12-O-tetradecanoylphorbol-13-acetate. The lack of increase in the number of cumulative papillomas per group due to benzoyl peroxide treatment suggests that benzoyl peroxide enhanced the progression of preexisting papillomas. The ability of benzoyl peroxide to enhance the progression of benign tumors to cancer should be considered when determining the human risk from exposure to this widely used chemical agent; in addition, biological assays specifically testing malignant progression may be essential and beneficial for determining an agent's carcinogenic risk.

Mouse skin tumors were induced by a single topical application of 7,12-dimethylbenzanthracene (DMBA), followed by biweekly promotion with 12- O -tetradecanoylphorbol-13-acetate (TPA). After 20 weeks of promotion, mice were treated twice weekly for 2 weeks with either ethylnitrosourea (ENU), N -methyl- N′ -nitro- N -nitrosoguanidine (MNNG) or TPA. Thereafter all groups were treated biweekly with TPA. The ENU-treated group had a higher percentage of animals with carcinomas and developed 217% more cumulative carcinomas per group than TPA-treated controls. The percentage of mice with carcinomas and the cumulative number of carcinomas per group in MNNG-treated mice was higher than TPA-treated controls but was less than ENU-treated mice. The ratio of cumulative carcinomas to cumulative papillomas in ENU treated, MNNG-treated and TPA-treated mice was 16%, 9% and 6%, respectively. Histological examination of tumors remaining at the termination of the experiment revealed the presence of keratoacanthomas, some of which stained positive for γ-glutamyltransferase (GGT), in the ENU-treated and MNNG-treated, but not the TPA-treated groups. The fact that no new papillomas developed during the progression stage indicated that enhanced carcinogenesis resulted from the progression of pre-existing tumors. Enhanced progression of benign skin tumors in mice by only a few treatments of an agent may serve as a potential model for studies into the mechanisms and the inhibition of malignant progression. The model also allows for a comparison of the potency of agents in enhancing malignant progression.

This report examines 18 surgically proven L3/4 herniated nucleus pulposus (HNP), all having myelogram, CT and adequate neurological evaluation. It will focus on four cases where the herniation involved the neural canal (intervertebral canal). Comparison to the 14 spinal canal central herniations will be made. The clinical findings for lateral L3/4 HNP allowed a preimaging diagnosis to be made in three of the four cases. In the central group the correct preimaging diagnosis was made one of the 14 cases (P less than 0.01). There are numerous reasons why the central L3/4 HNP preimaging diagnosis is inaccurate as well as difficult to establish and these reasons are discussed in detail. The myelographic and CT findings of the lateral L3/4 HNP are clearly elaborated. All herniations were extruded. They poorly responded to conservative management. The duration of illness, onset of pain to surgical disk removal, for the lateral herniations was 34.8 days and, 154.4 days for the central group (P less than 0.05). The myelogram is a disappointing test in the diagnosis of lateral L3/4 HNP, but highly accurate in spinal canal L3/4 HNP. CT is a preferred imaging test being virtually positive in all cases.

The in vivo behavior of cell cultures derived from normal and carcinogen-treated mouse epidermis was studied by implanting the cultures in a s.c. vascularized bed protected by a silicone chamber. Cells derived from normal adult mouse epidermis as well as cells derived from tumor-promoter-treated skin were unable to grow in these systems. Conversely, cell lines derived from skin initiated with single doses of N-methyl-N'-nitro-N-nitrosoguanidine or 9,10-dimethyl-1,2-benzanthracene proliferated in these chambers, reforming an epithelial structure. The type of structure in the chambers varied, ranging from formation of almost normal epithelia to atypical invasive behavior. The variable in vivo behavior among the different cell lines may be attributed to the initiation agent, the number of passages of the cultures, random genetic events, the strain of mouse, or a combination of these factors. Most of the cell types used in this study and all the cell lines that were able to grow in these chambers were selected for resistance to Ca-induced terminal differentiation. However, resistance to terminal differentiation according to the Ca2+ switch does not always correlate with the ability to grow in the chambers, since cell lines derived from spontaneous foci of resistance failed to grow in this system. These studies showed some of the possibilities of the SC silicone chambers to study the histogenic potential of cell lines derived from carcinogen-treated epidermis. This system also appears suitable to study the complex relationship between epidermal cells and specialized (dermal) stroma.

Night radiology is the practice of the in-hospital radiologist from 4:00 to 11:00 p.m. His duty is to keep the interpretation of radiographs current. At the medical center described, an average of 95 radiographic examinations per day are performed during the evening and at night; 60 of these require immediate interpretation. Night radiology was instituted because of the large number of unmonitored and uninterpreted films that had to be dealt with the following morning. The night radiology duty is seven consecutive nights and is rotated among all nine staff radiologists. Night radiology provides a service that the emergency department and the private physician can rely on and can use without hesitation, delay, or resistance.